Core E - Microvascular Complications Core The microvascular complications of type 1 and 2 diabetes are major causes of morbidity and mortality. Adequate murine models of these complications are critical to their understanding, treatment and prevention. Development and testing of murine models of diabetic microvasular complications has been slowed by the relative paucity of uniform phenotyping standards and methods. The Complications Core will help to overcome this barrier by providing validated, reproducible and standardized phenotyping of the 3 major microvascular complications: diabetic polyneuropathy (DPN), nephropathy (DN) and retinopathy (DR). The Microvascular Complications Core will make the phenotyping of mouse models of diabetic complications available, expeditious, affordable, effective, and convenient for individual investigators. In addition to providing education, consultation and advice regarding the analysis of mouse models of complications, the Core will provide phenotyping services using the specialized equipment that it operates. Specifically, the Core will provide assessment of murine DPN, DN and DR using clinical and anatomical assays for each complication and will also offer advanced phenotyping of models exhibiting each complication. DPN advanced testing will include phenotyping of models exhibiting neuropathy such as measures of cell death and oxidative stress in dorsal root ganglion (DRG) and peripheral nerve. DN advanced phenotyping will include measures of podocyte number, precise morphometric analysis of glomerular expansion, glomerular volume and tubulointerstitial fibrosis, EM morphometry of podocyte foot processes, immunohistochemical analysis of podocyte specific proteins, and glomerular isolation. DR advanced testing will include measures of retinal vascular permeability, retinal cell death and non-lethal measures of retinal morphology using optical coherence tomography and visual function using optokinetic response. A significant strength of the Complications Core is that all testing methods will be housed within one laboratory and that all three complications can be assessed in a single mouse. This will allow for the efficient flow and coordination of animal testing, data collection and ultimately tissue harvest. Many assays performed in conscious animals may be repeated over the course of the experiment while others will be performed immediately prior to euthanasia. All components of the Complications Core will work closely together and with client investigators to coordinate the phenotypic characterization of microvascular complications. This comprehensive approach will reveal commonalties and differences among complications as well as addressing the impact of specific gene alterations and treatment regimens.